Fibrinolytic treatment using recombinant tissue-type plasminogen activator (rt-PA) for staphylococcal infective...

Infective endocarditis (IE) is a severe illness characterized by vegetation of bacterial thrombosis. We hypothesized that adding recombinant tissue-type plasminogen activator (rt-PA) to antibiotics would contribute to good results in the treatment of IE. As an in vitro study, we injected labeled Staphylococcus aureus (S. aureus) and either rt-PA or PBS + plasminogen into a polydimethylsiloxane flow chamber with fibrin on a coverslip, and then performed immunofluorescent area assessment. As an in vivo experiment, IE model rats that had suffered mechanical damage in the aortic valve by catheter and revealed bacterial vegetation caused by S. aureus injection were treated with either a control, cefazolin (CEZ), rt-PA, or rt-PA + CEZ, for 7 days. Survival was assessed for 14 days after the appearance of vegetation, with daily monitoring of the vegetation by transthoracic echocardiography (TTE). The in vitro investigation showed that perfusion of rt-PA could detach S. aureus significantly more efficiently than PBS could. In the in vivo research, the rt-PA + CEZ group survived significantly longer than the other groups, and rt-PA + CEZ was more effective than CEZ in the dissolution of vegetation, as observed by TTE. In conclusion, adding rt-PA to antibiotic treatment could dissolve the vegetation component synergistically and improve the survival rate.